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Zircon Hf Isotope Mapping for Understanding Crustal Architecture and Its Controls on Mineralization during Early Cretaceous in the Southern Great Xing'an Range,NE China

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Journal of Earth Science 2024年第1期35卷 41-50页

作者： feng yuan Huanan Liu Shengjin Zhao Mingjing Fan State Key Laboratory of Geological Processes and Mineral Resources Collaborative Innovation Center for Exploration of Strategic Mineral ResourcesSchool of Earth ResourcesChina University of GeosciencesWuhan 430074China State Key Laboratory of Geological Processes and Mineral Resources School of Earth Sciences and ResourcesChina University of GeosciencesBeijing100083China No.10 Institute of Geological Exploration Inner Mongolia Bureau of Geology and Mineral ResourcesChifeng 024000China Key Laboratory of Metallogeny and Mineral Assessment Institute of Mineral ResourcesChinese Academy of Geological SciencesBeijing 100037China

Voluminous Early Cretaceous granitoids and associated large-scale ore deposits are distributed within the southern Great Xing'an Range(SGXR),NE China.Based on previously published geochronology and zircon Hf-isotope data,Hf isotope mapping is undertaken to improve our understanding of crustal architecture and its controls on ore deposits.The ore-related Early Cretaceous granitoids were sourced predominantly from juvenile crust,with the involvement of variable proportions of ancient crustal materials.The crustal architecture,as inferred from Hf isotopic contour maps,indicates two distinct Hf isotopic domains in SGXR,including(1)a higher-ε_(Hf)(+7 to+11)juvenile crust containing minor ancient crustal material,and(2)a lower-ε_(Hf)(+2 to+6)juvenile crust containing a greater proportion of ancient crustal materials.The Hf isotopic maps identify links between crustal architecture and regional metallogeny.Copper deposits and other deposits with significant Cu production are restricted mainly to the higher-ε_(Hf)juvenile crustal regions in the northern and eastern SGXR.Deposits dominated by other metals(e.g.,Mo,Sn,W,Pb,Zn,and Ag)occur mainly in the lower-ε_(Hf)juvenile crustal regions in the southern and western SGXR.Interaction between juvenile crust-derived melts and ancient crustal components played an important role on the distribution of various ore metals.

关键词： Hf isotope mapping crustal architecture large-scale Early Cretaceous granitoids distribution of ore deposits southern Great Xing'an Range zircon

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GNAS mutations suppress cell invasion by activating MEG3 in growth hormone–secreting pituitary adenoma

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Oncology Research 2024年第6期32卷 1079-1091页

作者： CHAO TANG CHUNYU ZHONG JUNHAO ZHU feng yuan JIN YANG YONG XU CHIyuan MA Department of Neurosurgery Affiliated Jinling HospitalMedical School of Nanjing UniversityNanjing210002China Department of Neurosurgery Children’s Hospital of Nanjing Medical UniversityNanjing210019China Affiliated Eye Hospital Nanjing Medical UniversityNanjing210029China Department of Neurosurgery Jinling HospitalSouthern Medical UniversityNanjing210002China Department of Neurosurgery Jinling HospitalNanjing Medical UniversityNanjing210002China

Approximately 30%–40%of growth hormone–secreting pituitary adenomas(GHPAs)harbor somatic activating mutations in GNAS(αsubunit of stimulatory G protein).Mutations in GNAS are associated with clinical features of smaller and less invasive tumors.However,the role of GNAS mutations in the invasiveness of GHPAs is unclear.GNAS mutations were detected in GHPAs using a standard polymerase chain reaction(PCR)sequencing procedure.The expression of mutation-associated maternally expressed gene 3(MEG3)was evaluated with RT-qPCR.MEG3 was manipulated in GH3 cells using a lentiviral expression system.Cell invasion ability was measured using a Transwell assay,and epithelial–mesenchymal transition(EMT)-associated proteins were quantified by immunofluorescence and western blotting.Finally,a tumor cell xenograft mouse model was used to verify the effect of MEG3 on tumor growth and invasiveness.The invasiveness of GHPAs was significantly decreased in mice with mutated GNAS compared with that in mice with wild-type GNAS.Consistently,the invasiveness of mutant GNASexpressing GH3 cells decreased.MEG3 is uniquely expressed at high levels in GHPAs harboring mutated GNAS.Accordingly,MEG3 upregulation inhibited tumor cell invasion,and conversely,MEG3 downregulation increased tumor cell invasion.Mechanistically,GNAS mutations inhibit EMT in GHPAs.MEG3 in mutated GNAS cells prevented cell invasion through the inactivation of the Wnt/β-catenin signaling pathway,which was further validated in vivo.Our data suggest that GNAS mutations may suppress cell invasion in GHPAs by regulating EMT through the activation of the MEG3/Wnt/β-catenin signaling pathway.

关键词： GHPAs GNAS mutation MEG3 β-catenin EMT

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Efficacy and safety of low-dose cyclophosphamide combined with lenvatinib, pembrolizumab and TACE for unresectable hepatocellular carcinoma:A single-center, prospective,single-arm clinical trial

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Chinese Journal of Cancer Research 2024年第2期36卷 114-123页

作者： Yupeng Ren Yuxuan Li Mingbo Cao Yongchang Tang feng yuan Gaoyuan Yang Zhiwei He Zheng Shi Xiaorui Su Zhicheng Yao Meihai Deng Department of Hepatobiliary Surgery the Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China Department of General Surgery Qilu HospitalShandong UniversityJinan 250012China Department of Hepatobiliary Surgery the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China Department of Hepatobiliary and Pancreatic Surgery the Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China

Objective: Unresectable hepatocellular carcinoma(uHCC) continues to pose effective treatment options. The objective of this study was to assess the efficacy and safety of combining low-dose cyclophosphamide with lenvatinib, pembrolizumab and transarterial chemoembolization(TACE) for the treatment of uHCC.Methods: From February 2022 to November 2023, a total of 40 patients diagnosed with uHCC were enrolled in this small-dose, single-center, single-arm, prospective study. They received a combined treatment of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE. Study endpoints included progression-free survival(PFS), objective response rate(ORR), and safety assessment. Tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors(mRECIST), while survival analysis was conducted through KaplanMeier curve analysis for overall survival(OS) and PFS. Adverse events(AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events(version 5.0).Results: A total of 34 patients were included in the study. The median follow-up duration was 11.2 [95% confidence interval(95% CI), 5.3-14.6] months, and the median PFS(mPFS) was 15.5(95% CI, 5.4-NA) months.Median OS(mOS) was not attained during the study period. The ORR was 55.9%, and the disease control rate(DCR) was 70.6%. AEs were reported in 27(79.4%) patients. The most frequently reported AEs(with an incidence rate >10%) included abnormal liver function(52.9%), abdominal pain(44.1%), abdominal distension and constipation(29.4%), hypertension(20.6%), leukopenia(17.6%), constipation(17.6%), ascites(14.7%), and insomnia(14.7%). Abnormal liver function(14.7%) had the most common grade 3 or higher AEs.Conclusions: A combination of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE is safe and effective for u HCC, showcasing a promising therapeutic strategy for managing uHCC.

关键词： Hepatocellular carcinoma lenvatinib low-dose cyclophosphamide pembrolizumab transarterial chemoembolization

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Unraveling the efficacy network: A network meta-analysis of adjuvant external beam radiation therapy methods after hepatectomy

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World Journal of Gastrointestinal Surgery 2024年第1期16卷 205-214页

作者： Gao-yuan Yang Zhi-Wei He Yong-Chang Tang feng yuan Ming-Bo Cao Yu-Peng Ren Yu-Xuan Li Xiao-Rui Su Zhi-Cheng Yao Mei-Hai Deng Department of Hepatobiliary Surgery The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630Guangdong ProvinceChina Department of General Surgery Qilu HospitalShandong UniversityJinan 250012Shandong ProvinceChina Department of General Surgery The First Affiliated HospitalGuangzhou Medical UniversityGuangzhou 511436Guangdong ProvinceChina Department of Hepatobiliary and Pancreatic Surgery The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630Guangdong ProvinceChina

BACKGROUND Primary liver cancer is a malignant tumor with a high recurrence rate that significantly affects patient prognosis.Postoperative adjuvant external radiation therapy(RT)has been shown to effectively prevent recurrence after liver cancer resection.However,there are multiple RT techniques available,and the differ-ential effects of these techniques in preventing postoperative liver cancer re-currence require further investigation.AIM To assess the advantages and disadvantages of various adjuvant external RT methods after liver resection based on overall survival(OS)and disease-free survival(DFS)and to determine the optimal strategy.METHODS This study involved network meta-analyses and followed the PRISMA guidelines.The data of qualified studies published before July 10,2023,were collected from PubMed,Embase,the Web of Science,and the Cochrane Library.We included relevant studies on postoperative external beam RT after liver resection that had OS and DFS as the primary endpoints.The magnitudes of the effects were determined using risk ratios with 95%confidential intervals.The results were analyzed using R software and STATA software.RESULTS A total of 12 studies,including 1265 patients with hepatocellular carcinoma(HCC)after liver resection,were included in this study.There was no significant heterogeneity in the direct paired comparisons,and there were no significant differences in the inclusion or exclusion criteria,intervention measures,or outcome indicators,meeting the assumptions of heterogeneity and transitivity.OS analysis revealed that patients who underwent stereotactic body radiotherapy(SBRT)after resection had longer OS than those who underwent intensity modulated radiotherapy(IMRT)or 3-dimensional conformal RT(3D-CRT).DFS analysis revealed that patients who underwent 3D-CRT after resection had the longest DFS.Patients who underwent IMRT after resection had longer OS than those who underwent 3D-CRT and longer DFS than those who underwent SBRT.CONCLUSION HCC patients who undergo liver cancer resec

关键词： Primary liver cancer Hepatocellular carcinoma Network meta-analysis External beam radiation therapy Stereotactic body radiotherapy Intensity modulated radiotherapy

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Development of a single transcript CRISPR/Cas9 toolkit for efficient genome editing in autotetraploid alfalfa

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The Crop Journal 2024年第3期12卷 788-795页

作者： Haixia Zhao Siyi Zhao Yingping Cao Xiping Jiang Lijuan Zhao Zhimeng Li Mengqi Wang Ruijuan Yang Chuanen Zhou Zhaoming Wang feng yuan Dongmei Ma Hao Lin Wenwen Liu Chunxiang Fu CAS Key Laboratory of Biofuels Shandong Provincial Key Laboratory of Energy GeneticsQingdao Institute of Bioenergy and Bioprocess TechnologyChinese Academy of SciencesQingdao 266101ShandongChina Shandong Energy Institute Qingdao 266101ShandongChina Qingdao New Energy Shandong Laboratory Qingdao 266101ShandongChina University of Chinese Academy of Sciences Beijing 100049China The Key Laboratory of Plant Development and Environmental Adaptation Biology Ministry of EducationSchool of Life SciencesShandong UniversityQingdao 266101ShandongChina Key Laboratory of Forage Breeding and Seed Production of Inner Mongolia Inner Mongolia M-Grass Ecology and Environment(Group)Co.Ltd.Hohhot 010016Inner MongoliaChina School of Ecology Environment Ningxia UniversityYinchuan 750021NingxiaChina Biotechnology Research Institute Chinese Academy of Agricultural SciencesBeijing 100081China

Alfalfa(Medicago sativa.L.)is a globally significant autotetraploid legume forage crop.However,despite its importance,establishing efficient gene editing systems for cultivated alfalfa remains a formidable challenge.In this study,we pioneered the development of a highly effective ultrasonic-assisted leaf disc transformation system for Gongnong 1 alfalfa,a variety widely cultivated in Northeast China.Subsequently,we created a single transcript CRISPR/Cas9(CRISPR_2.0)toolkit,incorporating multiplex gRNAs,designed for gene editing in Gongnong 1.Both Cas9 and gRNA scaffolds were under the control of the Arabidopsis ubiquitin-10 promoter,a widely employed polymeraseⅡconstitutive promoter known for strong transgene expression in dicots.To assess the toolkit’s efficiency,we targeted PALM1,a gene associated with a recognizable multifoliate phenotype.Utilizing the CRISPR_2.0 toolkit,we directed PALM1 editing at two sites in the wild-type Gongnong 1.Results indicated a 35.1%occurrence of editing events all in target 2 alleles,while no mutations were detected at target 1 in the transgenic-positive lines.To explore more efficient sgRNAs,we developed a rapid,reliable screening system based on Agrobacterium rhizogenes-mediated hairy root transformation,incorporating the visible reporter MtLAP1.This screening system demonstrated that most purple visible hairy roots underwent gene editing.Notably,sgRNA3,with an 83.0%editing efficiency,was selected using the visible hairy root system.As anticipated,tetra-allelic homozygous palm1 mutations exhibited a clear multifoliate phenotype.These palm1 lines demonstrated an average crude protein yield increase of 21.5%compared to trifoliolate alfalfa.Our findings highlight the modified CRISPR_2.0 system as a highly efficient and robust gene editing tool for autotetraploid alfalfa.

关键词： Alfalfa Gene editing CRISPR_2.0 toolkit Hairy root system Tetra-allelic homozygous mutants

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Severe liver injury and clinical characteristics of occupational exposure to 2-amino-5-chloro-N,3-dimethylbenzamide: A case series

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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 186-194页

作者： Meng-Xiao feng Hua Zou yuan-Qiang Lu Department of Emergency Medicine The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases of Zhejiang Province Hangzhou 310003China Occupational Health and Radiation Protection Institute Zhejiang Provincial Center for Disease Control and PreventionHangzhou 310051China

Background:The 2-amino-5-chloro-N,3-dimethylbenzamide is a key intermediate in the synthesis of pesticides and pharmaceuticals.However,no literature currently exists on 2-amino-5-chloro-N,3-dimethylbenzamide poisoning in humans.This study aimed to reveal the health hazard of this chemical for humans and summarize the clinical characteristics of patients with occupational 2-amino-5-chloro-N,3-dimethylbenzamide poisoning.Methods:This observational study included four patients with 2-amino-5-chloro-N,3-dimethylbenzamide poisoning from June 2022 to July 2022.The entire course of the incidents was described in detail.Blood 2-amino-5-chloro-N,3-dimethylbenzamide concentrations were detected by a mass spectrometer.Hema-toxylin and eosin staining was performed to assess liver injury,and immunofluorescence was used to evaluate hepatic mitophagy.Results:The 2-amino-5-chloro-N,3-dimethylbenzamide powder(99%purity)entered the human body mainly via the skin and respiratory tract due to poor personal protective measures.The typical course of 2-amino-5-chloro-N,3-dimethylbenzamide poisoning was divided into latency,rash,fever,organic dam-age,and recovery phases in accordance with the clinical evolution.Rash and fever may be the important premonitory symptoms for further organ injuries.The chemical was detected in the blood of all patients and caused multiple organ injuries,predominantly liver injury,including kidney,myocardium,and micro-circulation.Three patients recovered smoothly after comprehensive treatments,including artificial liver therapy,continuous renal replacement therapy,glucocorticoids,and other symptomatic and supportive treatments.One patient survived by liver transplantation.The postoperative pathological findings of the removed liver showed acute liver failure,and immunofluorescence staining confirmed the abundance of mitophagy in residual hepatocytes.Conclusions:This study is the first to elaborate the clinical characteristics of patients with 2-amino-5-chloro-N,3-dimethylbenzamide poisoning.The chemical enter

关键词： 2-amino-5-chloro-N,3-dimethylbenzamide Poisoning Clinical characteristics Liver injury

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A Trust Evaluation Mechanism Based on Autoencoder Clustering Algorithm for Edge Device Access of IoT

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Computers, Materials & Continua 2024年第2期78卷 1881-1895页

作者： Xiao feng Zheng yuan Cyber Security Academy Beijing University of Posts and TelecommunicationsBeijing100876China Department of Cyberspace Security Beijing Electronic Science and Technology InstituteBeijing100070China State Grid Info-Telecom Great Power Science and Technology Co. Ltd.Beijing102211China

First,we propose a cross-domain authentication architecture based on trust evaluation mechanism,including registration,certificate issuance,and cross-domain authentication processes.A direct trust evaluation mechanism based on the time decay factor is proposed,taking into account the influence of historical interaction records.We weight the time attenuation factor to each historical interaction record for updating and got the new historical record data.We refer to the beta distribution to enhance the flexibility and adaptability of the direct trust assessment model to better capture time trends in the historical record.Then we propose an autoencoder-based trust clustering algorithm.We perform feature extraction based on autoencoders.Kullback leibler(KL)divergence is used to calculate the reconstruction error.When constructing a convolutional autoencoder,we introduce convolutional neural networks to improve training efficiency and introduce sparse constraints into the hidden layer of the autoencoder.The sparse penalty term in the loss function measures the difference through the KL divergence.Trust clustering is performed based on the density based spatial clustering of applications with noise(DBSCAN)clustering algorithm.During the clustering process,edge nodes have a variety of trustworthy attribute characteristics.We assign different attribute weights according to the relative importance of each attribute in the clustering process,and a larger weight means that the attribute occupies a greater weight in the calculation of distance.Finally,we introduced adaptive weights to calculate comprehensive trust evaluation.Simulation experiments prove that our trust evaluation mechanism has excellent reliability and accuracy.

关键词： Cross-domain authentication trust evaluation autoencoder

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A versatile model with three-dimensional triangular lattice for unconventional transport and various topological effects

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National Science Review 2024年第1期11卷 204-214页

作者： Jing-Yang You Gang Su yuan Ping feng Department of Physics National University of Singapore Kavli Institute for Theoretical Sciences and CAS Center for Excellence in Topological Quantum Computation University of Chinese Academy of Sciences Centre for Advanced 2D Materials National University of Singapore

The finite Berry curvature in topological materials can induce many subtle phenomena, such as the anomalous Hall effect(AHE), spin Hall effect(SHE), anomalous Nernst effect(ANE), non-linear Hall effect(NLHE) and bulk photovoltaic effects. To explore these novel physics as well as their connection and coupling, a precise and effective model should be developed. Here, we propose such a versatile model—a 3D triangular lattice with alternating hopping parameters, which can yield various topological phases,including kagome bands, triply degenerate fermions, double Weyl semimetals and so on. We reveal that this special lattice can present unconventional transport due to its unique topological surface states and the aforementioned topological phenomena, such as AHE, ANE, NLHE and the topological photocurrent effect. In addition, we also provide a number of material candidates that have been synthesized experimentally with this lattice, and discuss two materials, including a non-magnetic triangular system for SHE, NLHE and the shift current, and a ferromagnetic triangular lattice for AHE and ANE. Our work provides an excellent platform, including both the model and materials, for the study of Berry-curvature-related physics.

关键词： three-dimensional triangular lattice different topological phases various topological effects Berry curvature

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Recent Advances in Deciphering the Mechanisms and Biological Functions of DNA Demethylation

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Chinese Journal of Chemistry 2024年第6期42卷 645-651页

作者： Yang feng Sheng-Jun Chen Bi-feng yuan Key Laboratory of Aquatic Product Processing Ministry of Agriculture and Rural AffairsNational R&D Center for Aquatic Product ProcessingSouth China Sea Fisheries Research InstituteChinese Academy of Fishery SciencesGuangzhouGuangdong510300 China School of Public Health Research Center of Public HealthRenmin Hospital of Wuhan UniversityWuhan UniversityWuhanHubei430071 China

5-Methylcytosine (5mC) is a dynamic and reversible epigenetic modification in genomic DNA of higher eukaryotes.It has been well-established that the demethylation of 5mC occurs through the ten-eleven translocation (TET)-mediated oxidation of 5mC followed by thymine DNA glycosylase (TDG)-initiated base excision repair (BER).Recent findings also have identified an alternative pathway of DNA demethylation.In this pathway,TET enzymes directly oxidize 5mC to form 5-formylcytosine (5fC) or 5-carboxylcytosine (5caC).These modified bases can undergo direct deformylation or decarboxylation,respectively.Additionally,DNA demethylation can also occur through the deamination of 5mC and 5hmC,resulting in the production of thymine and 5-hydroxymethyluracil (5hmU),respectively.Various DNA demethylation pathways possess critical functional implications and roles in biological processes.This Recent Advances article will focus on the studies of mechanisms and biological functions of DNA demethylation,shedding light on the reversible nature of the epigenetic modification of 5mC.

关键词： Epigenetics DNA DNA methylation 5-Methylcytosine Demethylation Mechanisms Biological functions C—C bond cleavage Mass spectrometry

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NCAD v1.0: a database for non-coding variant annotation and interpretation

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Journal of Genetics and Genomics 2024年第2期51卷 230-242页

作者： Xiaoshu feng Sihan Liu Ke Li fengxiao Bu Huijun yuan Institute of Rare Diseases West China HospitalSichuan UniversityChengduSichuan 610044China

The application of whole genome sequencing is expanding in clinical diagnostics across various genetic disorders, and the significance of non-coding variants in penetrant diseases is increasingly being demonstrated. Therefore, it is urgent to improve the diagnostic yield by exploring the pathogenic mechanisms of variants in non-coding regions. However, the interpretation of non-coding variants remains a significant challenge, due to the complex functional regulatory mechanisms of non-coding regions and the current limitations of available databases and tools. Hence, we develop the non-coding variant annotation database (NCAD, http://***/), encompassing comprehensive insights into 665,679,194 variants, regulatory elements, and element interaction details. Integrating data from 96 sources, spanning both GRCh37 and GRCh38 versions, NCAD v1.0 provides vital information to support the genetic diagnosis of non-coding variants, including allele frequencies of 12 diverse populations, with a particular focus on the population frequency information for 230,235,698 variants in 20,964 Chinese individuals. Moreover, it offers prediction scores for variant functionality, five categories of regulatory elements, and four types of non-coding RNAs. With its rich data and comprehensive coverage, NCAD serves as a valuable platform, empowering researchers and clinicians with profound insights into non-coding regulatory mechanisms while facilitating the interpretation of non-coding variants.

关键词： Non-coding variants Annotation Variant interpretation Database

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